title: Bone marrow deficiency of TRPC3 channel reduces early lesion burden and necrotic core of advanced plaques in a mouse model of atherosclerosis.
abstract: OBJECTIVE
  Macrophage apoptosis plays a determinant role in progression of atherosclerotic lesions. An important goal in atherosclerosis research is to identify new components of macrophage apoptosis that can eventually be exploited as molecular targets in strategies aimed at manipulating macrophage function in the lesion. In the previous work from our laboratory, we have shown that transient receptor potential canonical 3 (TRPC3) channel is an obligatory component of survival mechanisms in human and murine macrophages and that TRPC3-deficient non-polarized bone marrow-derived macrophages exhibit increased apoptosis, suggesting that in vivo TRPC3 might influence lesion development. In the present work, we used a bone marrow transplantation strategy as a first approach to examine the impact of macrophage deficiency of TRPC3 on early and advanced atherosclerotic lesions of Apoe(-/-) mice.
  
  
  RESULTS
  After 3 weeks of high-fat diet, lesions in mice transplanted with bone marrow from Trpc3(-/-) donors were smaller and with reduced cellularity than controls. Advanced lesions from these mice exhibited reduced necrotic core, less apoptotic macrophages, and increased collagen content and cap thickness. In vitro, TRPC3-deficient macrophages polarized to the M1 phenotype showed reduced apoptosis, whereas both M1 and M2 macrophages had increased efferocytic capacity.
  
  
  CONCLUSIONS
  Bone marrow deficiency of TRPC3 has a dual beneficial effect on lesion progression by reducing cellularity at early stages and necrosis in the advanced plaques. Our findings represent the first evidence for a role of a member of the TRPC family of cation channels in mechanisms associated with atherosclerosis.
authors.affiliation: Department of Physiology and Pharmacology and Center for Diabetes and Endocrine Research, University of Toledo Health Science Campus, 3000 Transverse Dr, Toledo, OH 43614, USA;
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Tano
authors.forename: Sumeet
authors.initials: S
authors.lastname: Solanki
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lee
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smedlund
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: Guillermo
authors.initials: G
authors.lastname: Vazquez
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009336:Necrosis; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel
keywords: Atherosclerosis; Calcium channels; Macrophage apoptosis; TRPC3 channel